Genetic variation of XPA gene and risk of cancer: A systematic review and pooled analysis

Abstract

XPA, a zinc-finger DNA-binding protein, play an important role in both global genome and transcription-coupled repair pathways. XPA 24G>A polymorphism was identified in the 5 0 noncoding region, located four nucleotides upstream of the ATG start codon. Previous studies have shown that this polymorphism may affect mRNA tertiary structure and stability and play a role in susceptibility to cancer. However, the results remained controversial. To derive a more precise estimation of association between this polymorphism and risk of different types of cancer, we performed a meta-analysis based on 36 case-control or case-cohort studies, including a total of 11,700 cases and 15,033 controls. We used odds ratios with 95% confidence intervals to assess the strength of the association. Overall, no significantly elevated cancer risk was found in all genetic models when eligible studies were pooled into the meta-analysis. In the stratified analyses, we found that individuals with A-allele had a higher risk of lung cancer (AA versus GG: OR 5 1.25, 95% CI 5 1.09-1.43; recessive model: OR 5 1.31, 95% CI 5 1.16-1.48). When stratified by ethnicity, significantly elevated risks were observed among Asian populations (AA versus GG: OR 5 1.31, 95% CI 5 1.01-1.70; dominant model: OR 5 1.14, 95% CI 5 1.00-1.30). This meta-analysis suggests that XPA 24G>A polymorphism is associated with increased lung cancer risk and may be a low-penetrant risk factor in Asian ethnicity for cancer development.

Association of the XPA A23G polymorphism with the risk of head and neck carcinomas: Evidence from 5,491 subjects

“…The A23G polymorphism regulated XPA gene expression through transcriptional and post-transcriptional control mechanisms. XPA A23G genetic variations thus have the potential to influence protein function and subsequently DNA repair capacity (8)(9)(10). Several studies on the association of the XPA A23G polymorphism with HNSCC susceptibility have been published (11-18).…”

“…Additionally, XPA is involved in a step of damage recognition, and plays a key role in global genome and transcription-coupled repair pathways (7). A common single-nucleotide polymorphism of XPA A23G, rs1800975, is an A-to-G point mutation in the 5' noncoding region of four nucleotides upstream of the start codon of XPA, which has been identified and extensively researched (8)(9)(10).…”

Head and Neck Squamous Cell Carcinoma: Prognosis using molecular approach

“…The Xeroderma Pigmentosum Complementation group A (XPA) gene located at chromosome number 9 (9q23.3) encodes a hydrophobic zinc finger protein present in the nucleus and involved in both the global genome and transcription coupled repair functions of the NER pathway [38]. XPA binds with single stranded DNA binding protein replication protein A (RPA), transcription factor TFIIH, excision repair cross complementing group 1 (ERCC1), xeroderma pigmentosum group F (XPF), and mediates damage recognition [38].…”

“…XPA binds with single stranded DNA binding protein replication protein A (RPA), transcription factor TFIIH, excision repair cross complementing group 1 (ERCC1), xeroderma pigmentosum group F (XPF), and mediates damage recognition [38]. Previously, studies have shown that polymorphism in XPA influences the stability of mRNA transcription factors and may play a crucial rule in susceptibility to cancer [38]. XPA single base substitution (G>A) was identified in the 5' non coding region and is the most widely reported polymorphism associated with different cancer [39].…”

Generation of Xeroderma Pigmentosum-A Patient-Derived Induced Pluripotent Stem Cell Line for Use As Future Disease Model

“…The genes responsible for these XP groups have been identified and their roles and NER mechanisms have been clarified at the molecular level (Fassihi, 2013;Lehmann et al, 2011). In a step of damage recognition, the XPA gene encodes a zinc finger motif protein that binds to damaged DNA by interaction with replication protein A (RPA), transcription factor IIH (TFIIH), and the excision repair cross-complementing group 1-xeroderma pigmentosum group F (ERCC1-XPF) protein complex (Batty and Wood, 2000;Ding et al, 2012;Rademakers et al, 2003). In addition, recent research indicates that the Ras association (RalGDS/ AF-6) domain family member 1A (RASSF1A) tumor suppressor forms a complex with the XPA protein and regulates XPA-mediated DNA repair (Donninger et al, 2015).…”